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DCCT: Glucose variability not associated with development, progression of microvascular complications
Beyond the influence of HbA1c, within-day glycemic variability does not play an apparent role in the development of microvascular complications, according to a new analysis of data from the Diabetes Control and Complications Trial.
“The current analyses differ from previous analyses examining the potential effects of glycemic variability, independent from mean glycemia, on complications during the DCCT, by including additional assessments of glycemic variability and more complete glucose profiles through multiple imputation methods,” John M. Lachin, ScD, co-director of The Biostatistics Center at George Washington University in Rockville, Maryland, and colleagues wrote. “Although the prior analyses of these data also showed no association of within-day measures of variability
with long-term complications, they suffered from the large fraction of incomplete quarterly profiles.
While overall compliance in the DCCT was high, completion of seven-point glucose profile collections were problematic during the trial; at each of the seven time points, between 15% and 18% of glucose values were missing, according to researchers, though virtually all HbA1c data were complete. In a new analysis, Lachin and colleagues applied multiple imputation to estimate missing blood glucose profile values based on other observed measurements to increase statistical validity. Using these methods, researchers evaluated the association of within-day mean blood glucose and its components with glycated albumin and HbA1c, and the association of each with hypoglycemia and microvascular outcomes. Measures of variability included the within-day and updated mean (over time) of the SD, mean amplitude of glycemic excursions (MAGE), and M-value, and the longitudinal within-day, between-day and total variances. Researchers used Cox proportional hazards models to assess the association of each measure of glycemic variation, as a time-dependent covariate, with the risks for retinopathy and nephropathy, and a longitudinal logistic regression model to assess any association with cardiovascular autonomic neuropathy.
After adjusting for within-day mean blood glucose, no measure of within-day variability was associated with any retinopathy, microalbuminuria or cardiovascular autonomic neuropathy.
Only the longitudinal mean M-value (over time) was significantly associated with microalbuminuria when adjusted for the longitudinal mean blood glucose and corrected for multiple tests using the Holm procedure, the researchers wrote.
“Overall, the measures of glycemic variability based on the complete quarterly seven-point glucose profile data sets fail to provide strong or consistent evidence that glycemic variability contributes to the risk of development or progression of microvascular complications beyond that contributed by the mean level of glucose,” the researchers wrote. – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.